Identification of patients at risk of developing left ventricular (LV) remodeling and dysfunction after acute myocardial infarction (MI) would represent a major step forward towards personalized healthcare. Indeed, these patients could benefit from improved treatment and follow-up, such as the treatment with anti-remodeling drugs which have shown some ability to reduce LV remodeling and dysfunction after experimental MI (von Lueder T G, et al. Circulation: Heart Failure. 2015; 8:71-78). However, predicting outcome after MI is a challenging task. Circulating biomarkers such as the markers of cardiac injury creatine phosphokinase (CPK) and cardiac troponins (cTn), or the stress markers brain natriuretic peptides (BNP) have proven to be useful in some circumstances but have serious limitations due to lack of specificity (Jaffe A S, et al. J Am Coll Cardiol. 2011; 58:1819-1824) and stability in the few hours following MI (Talwar S, et al. Eur Heart J. 2000; 21:1514-1521). Therefore, novel biomarkers are required.
The bloodstream is the reservoir of biomarkers. Biomarkers have been traditionally discovered in the cell-free compartment of the blood. In recent years, analysis of transcriptomic profiles of peripheral blood cells allowed the identification of candidate prognostic biomarkers of MI among the RNA family. Initial studies focused on protein-coding RNAs. More recent investigations revealed that non-protein coding RNAs, also known as non-coding RNAs, may also be useful in this prospect. Non-coding RNAs occupy a significant part of our genome. Indeed, while more than 80% of the human genome is transcribed, less than 2% is subsequently translated into proteins. MicroRNAs (miRNAs) have been the first class of non-coding RNAs reported for their biomarker value and for their ability to predict LV dysfunction after MI. Later on, non-coding RNAs longer than 200 nucleotides and named long non-coding RNAs (IncRNAs), either measured in peripheral blood cells or in plasma, have also shown some predictive value after MI (reviewed in Devaux Y et al. Nat Rev Cardiol. 2015; 12:415-425).
Circular RNAs (circRNAs) constitute another arm of the family of non-coding RNAs. Their origin is diverse. They can be produced by the formation of a covalent link between 5′ and 3′ extremities of exons (exonic circRNAs) or introns (intronic circRNAs). Furthermore, they can be formed by a back-splicing reaction linking exons of protein-coding genes. Exon-intron circRNAs are generated when introns are retained during the circularization of exons. Unlike most IncRNAs, circRNAs are abundant, conserved and stable. In the mammalian brain, circRNAs are dynamically regulated. The function of circRNAs is still poorly characterized and the role of circRNAs in the heart is unknown. One study has reported an association between a circRNA (a circular form of the IncRNA ANRIL—antisense non-coding RNA in the INK4 locus) and the risk of atherosclerosis (Burd C E, et al. PLoS Genet. 2010; 6:e1001233).